Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis.
OBJECTIVE
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that occasionally progresses to cirrhosis but usually has a benign course. The aim of this study was to investigate the role of the hemochromatosis mutation Cys282Tyr in development of the mild hepatic iron overload found in some patients with NASH and its association with hepatic damage in these patients.


METHODS
Fifty-one patients with NASH were studied. The presence of the Cys282Tyr mutation was tested in all patients, and the data were analyzed with respect to the histological grade of steatosis, inflammation, Perls' staining, hepatic iron concentration (HIC), and serum iron indices.


RESULTS
Thirty-one percent of patients with NASH were either homozygous or heterozygous for the Cys282Tyr mutation. This mutation was significantly associated with Perls' stain grade (P < 0.005), HIC (P < 0.005), and transferrin saturation percentage (P < 0.005) but not with serum ferritin levels. Linear regression analysis showed that increased hepatic iron (Perls' stain or HIC) had the greatest association with the severity of fibrosis (P < 0.0001).


CONCLUSIONS
The Cys282Tyr mutation is responsible for most of the mild iron overload found in NASH and thus has a significant association with hepatic damage in these patients. Heterozygosity for the hemochromatosis gene mutation therefore cannot always be considered benign.
George
D K
DK
Clinical Sciences Unit, Queensland Institute of Medical Research, Brisbane, Australia.
Goldwurm
S
S
MacDonald
G A
GA
Cowley
L L
LL
Walker
N I
NI
Ward
P J
PJ
Jazwinska
E C
EC
Powell
L W
LW
D000328:Adult; D002908:Chronic Disease; D015331:Cohort Studies; D005218:Fat Necrosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D005234:Fatty Liver / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005819:Genetic Markers; D006432:Hemochromatosis / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012737:Sex Factors
D005819:Genetic Markers